This protocol uses color and power Doppler ultrasonography, volumetric MRI and other advanced MR imaging techniques (e.g., diffusion tensor MRI, tagging MRI) to address several important issues. These include: (1) the compressibility of the human tongue and its common, yet untested, reference as a muscular hydrostat; (2) task-induced interactions between lingual musculature and vasculature and region-specific vascular demands; (3) changes in lingual fiber orientation and strain distribution as a function of contraction tasks; and (4) effects of aging, disease, and exercise on lingual myoarchitecture and structure-function integration. By quantitatively addressing these issues, this protocol will contribute to a better understanding of the functional myoarchitectural and biomechanical intricacies of the in vivo human tongue. In the area of lingual volumetry, our multi-slice volumetric MRI studies have identified significant task-induced tongue volume changes in vivo. We have successfully validated our segmentation and volume estimation method using ex vivo models. The consistent finding of volume increase during maximum voluntary linguopharyngeal contractions raises question about the concept of the tongue as a muscular hydrostat. In the area of lingual morphology, we have proven that through our novel regularization method (based on normalized convolution) used with a new skewness similarity measure for segmentation, we can optimally analyze our diffusion tensor MRI data to visualize the complex compartmentalized lingual musculature in 3D. Our method, specifically, has enabled us to maintain the boundaries between linear and planar tensor regions; estimate the orientation of muscle fibers based on diffusivity characteristics; and delineate in detail the intrinsic and extrinsic tongue muscle compartments in fresh excised calf tongues. To our knowledge, we are the first group to demonstrate this feasibility. While studying lingual morphology using diffusion tensor MRI, we conducted additional experiments using constant b-value/constant gradient with varying diffusion intervals. We found cylindrically restricted and non-restricted diffusion, which enabled the estimation of restricting compartment size and volume fraction. To our knowledge, we are the first group to demonstrate apparent restricted water diffusion in muscle tissues. Continuation in this direction may open an avenue for measuring cellular morphological changes in muscle tissues. In the area of lingual hemodynamics, we have compared the hyperemia patterns in three lingual arterial sites, induced by maximum voluntary isometric contraction (MVIC) tasks, with the reperfusion characteristics of dry swallows. Through vessel diameter, flow volume, velocity, and vessel resistance measurements, we have found that dry swallows have significantly faster post-swallow onset of reperfusion and return to baseline pattern. Although the increase in vessel diameter post-swallow is similar to that measured post-MVIC, flow volumes and velocities are lower. These findings suggest much more efficient patterns of lingual flow recovery for swallowing and a vasculature highly tuned for endurance and fatigue resistance. In the area of lingual deformation, our in vivo tagged MRI studies of the tongue during gated effortful swallows have demonstrated: (1) moderate to moderately high positive strain (tissue expansion) in anterior and mid tongue across subjects; (2) mild tissue expansion in genioglossus; (3) striking difference across subjects in strain type and magnitude in tongue base; and (4) regional specificity in the determinants of deformation gradient tensors. These findings suggest mechanistically different task accommodation strategies and task-induced regional volume changes. Our multi-slice tagged MRI with assumption-free analysis holds considerable promise for a better understanding of 3D lingual functionall mechanics. This protocoll will continue to address issues related to the structure-function relationships of the human tongue and gain insights into the intricacies of lingual anatomy, volumetry, hemodynamics, kinematics, kinetics, and functional mechanics in health, aging, disease, and exercise. We hope to ultimately develop innovative, physiologically sound, and biologically realistic treatment techniques for lingual sensorimotor deficits and help our patients regain functional movement and control of the tongue in swallowing and speech.